The stem cell adjuvant with Exendin-4 repairs the heart after myocardial infarction via STAT3 activation.
The stem cell adjuvant with Exendin-4 repairs the heart after myocardial infarction via STAT3 activation.
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Exendin-4干细胞佐剂通过STAT3激活修复心肌梗塞后的心脏
DOI：
10.1111/jcmm.12272
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发表时间：
2014-07
影响因子：
5.3
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Liu J;Wang H;Wang Y;Yin Y;Du Z;Liu Z;Yang J;Hu S;Wang C;Chen Y
缺血心肌细胞存活率低是干细胞治疗的主要障碍。Exendin-4基于其多效性而具有潜在的心脏保护作用。本研究探讨Exendin-4联合脂肪干细胞(ADSCs)能否提高干细胞存活率，促进心肌梗死后的心肌修复。成年雄性SD大鼠结扎左前降支造成心肌梗死(MI)。将携带双融合报告基因[萤火虫荧光素酶和红色单体荧光蛋白(fluc-MRFP)]的ADSCs快速注射到Exendin-4治疗或不治疗的大鼠心肌梗死边缘区。体内纵向生物发光成像显示，Exendin-4提高了移植的ADSCs的存活率。此外，添加Exendin-4佐剂的ADSCs可减少氧化应激、细胞凋亡和纤维化。它们还改善了心肌活力和心功能，并增加了ADSCs在体内向心肌细胞和血管平滑肌细胞的分化率。然后，将ADSCs暴露于过氧化氢/血清剥夺(H_2O_2/SD)中以模拟体外缺血环境。结果表明，Exendin-4可减少ADSCs的凋亡，增强其旁分泌作用。此外，Exendin-4还通过Akt和ERK1/2的磷酸化激活信号转导和转录激活因子3(STAT3)。此外，Exendin-4还增加了ADSCs抗凋亡蛋白Bcl2，但降低了促凋亡蛋白Bax。综上所述，Exendin-4可通过Akt和ERK1/2的磷酸化激活STAT3，提高移植ADSCs的存活率和治疗效果。本研究提示Exendin-4在干细胞心脏再生中具有潜在的应用前景。
The poor survival of cells in ischaemic myocardium is a major obstacle for stem cell therapy. Exendin-4 holds the potential of cardioprotective effect based on its pleiotropic activity. This study investigated whether Exendin-4 in conjunction with adipose-derived stem cells (ADSCs) could improve the stem cell survival and contribute to myocardial repairs after infarction. Myocardial infarction (MI) was induced by the left anterior descending artery ligation in adult male Sprague-Dawley rats. ADSCs carrying double-fusion reporter gene [firefly luciferase and monomeric red fluorescent protein (fluc-mRFP)] were quickly injected into border zone of MI in rats treated with or without Exendin-4. Exendin-4 enhanced the survival of transplanted ADSCs, as demonstrated by the longitudinal in vivo bioluminescence imaging. Moreover, ADSCs adjuvant with Exendin-4 decreased oxidative stress, apoptosis and fibrosis. They also improved myocardial viability and cardiac function and increased the differentiation rates of ADSCs into cardiomyocytes and vascular smooth muscle cells in vivo. Then, ADSCs were exposed to hydrogen peroxide/serum deprivation (H2O2/SD) to mimic the ischaemic environment in vitro. Results showed that Exendin-4 decreased the apoptosis and enhanced the paracrine effect of ADSCs. In addition, Exendin-4 activated signal transducers and activators of transcription 3 (STAT3) through the phosphorylation of Akt and ERK1/2. Furthermore, Exendin-4 increased the anti-apoptotic protein Bcl-2, but decreased the pro-apoptotic protein Bax of ADSCs. In conclusion, Exendin-4 could improve the survival and therapeutic efficacy of transplanted ADSCs through STAT3 activation via the phosphorylation of Akt and ERK1/2. This study suggests the potential application of Exendin-4 for stem cell–based heart regeneration.
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影响因子：
24
作者：
Li, Zongjin;Lee, Andrew;Huang, Mei;Chun, Hyung;Chung, Jaehoon;Chu, Pauline;Hoyt, Grant;Yang, Phillip;Rosenberg, Jarrett;Robbins, Robert C.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
影响因子：
7.7
作者：
Mukai E;Fujimoto S;Sato H;Oneyama C;Kominato R;Sato Y;Sasaki M;Nishi Y;Okada M;Inagaki N
通讯作者：
Inagaki N
影响因子：
37.8
作者：
Cao, F;Lin, S;Wu, JC
通讯作者：
Wu, JC
影响因子：
18.2
作者：
Mazo, Manuel;Planat-Benard, Valerie;Prosper, Felipe
通讯作者：
Prosper, Felipe
DOI：
10.1146/annurev-cellbio-101011-155739
发表时间：
2012
影响因子：
11.3
作者：
Kikuchi K;Poss KD
通讯作者：
Poss KD